Understanding Neurodegenerative Mechanisms in Parkinson’s Disease Genetic cases linked with Parkinson’s disease (PD) have helped us understand how cells die in PD. Dysfunction of organelles including the proteasome, mitochondria and lysosome, as well as oxidative stress contribute to cell death in PD. We have developed cell models of PD that take into account the different factors that contribute to PD pathology to further our understanding of cell death mechanisms in sporadic and familial cases of PD. Our studies have demonstrated that mitochondria are central to the pathology of PD. On-going studies in the lab are focussed on understanding how mitochondrial dysfunction is affected in PD. We are also testing novel neuroprotective treatment targets in animal models of PD. Mechanisms Underlying Symptoms of Parkinson’s Disease In Parkinson’s disease (PD), as a consequence of slow and progressive degeneration of the dopaminergic projections from the substantia nigra pars compacta (SNc) to the striatum, function of the striatum is negatively impacted, causing dysregulation of basal ganglia circuitry, which drives abnormalities in basal ganglia function, which underpins the symptoms of PD. To understand how symptoms of PD are generated in the striatum, we are using rodent models of Parkinson’s disease to tease out the molecular and cellular abnormalities in the striatal output pathways. These studies largely involve genetic manipulation as well as biochemical and electrophysiological techniques. Specifically we are interested in determining how synaptic proteins and synaptic plasticity contribute to symptoms of PD.